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ORLANDO, Fla. — New research is giving people with obstructive sleep apnea (OSA) a reason to hope for a more convenient treatment: a pill that improved upper airway muscle dysfunction and reduced apnea-hypopnea index (AHI) scores among 324 people taking AD109 vs 322 taking a placebo for 6 months.

OSA can be highly inconvenient for people struggling to get a healthy night’s sleep, affecting quality of life for them and their sleep partners. Also, existing treatments like continuous positive airway pressure devices can be cumbersome and difficult for some patients to accept and adhere to over the long term.

An oral treatment could improve these challenges. AD109 is a fixed-dose pill containing the norepinephrine reuptake inhibitor, atomoxetine, and the antimuscarinic agent, aroxybutynin.

“The profound reduction in sleep apnea-specific hypoxic burden, which was 42% in an intent-to-treat analysis and 60% in the on-treatment analysis, was impressive,” said lead study author Patrick J. Strollo Jr, MD, professor of medicine and clinical and translational science, Department of Medicine Service, Veteran Affairs Pittsburgh Healthcare System and the University of Pittsburgh, Pittsburgh. “If approved by the FDA, this medication could be another tool in the toolbox for treating obstructive sleep apnea.”

Strollo presented the results of the SynAIRgy trial (NCT05813275) at the American Thoracic Society (ATS) 2026 International Conference. Two journal reports were simultaneously publishedon May 18, 2026, in the American Journal of Respiratory and Critical Care Medicine: the full study and an explainer article on the mechanisms of how AD109 works, including minimizing airway collapsibility and improving the apnea-hypopnea index.

Serious Health Outcomes Possible

People with OSA, the most common sleep disorder, experience recurrent upper airway collapse episodes. These events lead to repeated breathing interruptions and decreases in oxygen saturation. This intermittent hypoxia is also linked to risks including cardiovascular and cerebrovascular diseases, metabolic dysfunction, neurocognitive impairment, and increased mortality, the researchers noted.

Some people with OSA lack the classic symptoms such as excessive daytime sleepiness, loud snoring, or abrupt awakenings, but remain at risk for the serious adverse health outcomes. In the current research, only participants who had symptomatic OSA at baseline experienced a significant improvement from AD109.

The current study builds on previous findings that showed targeting neuromuscular dysfunction can reduce airway obstructions and improve oxygenation associated with OSA. In these prior reports, symptomatic patients also reported improvements in fatigue, sleepiness, and snoring more often than participants taking a placebo.

Dual Pill, Dual Effect?

Strollo and colleagues hypothesized that some people are more susceptible to airway collapse during sleep, and that AD109 could help this group by boosting noradrenergic activity while also reducing muscarinic inhibition.

The multicenter SynAIRgy trial assessed the safety and efficacy of AD109 in adults with mild-to-moderate OSA. All participants were unable or unwilling to use positive airway pressure therapy. The investigators randomly assigned the 646 participants to AD109 or placebo. OSA was mild in 35%, moderate in 42%, and severe in 23%. The median age was 58 years, 49% were women, and mean BMI was 32.4.

Key Findings

The primary study outcome was the mean change in AHI from baseline to 26 weeks. At baseline, the mean AHI score was 20 events/h.

The researchers found a statistically significant median AHI score reduction of 6.5 fewer events/h with treatment vs 1.4 fewer events/h with placebo in an intent-to treat analysis. A study model estimated this decrease as 44% in the AD109 group vs 18% in the placebo group (P < .0001).

In an on-treatment analysis, median AHI decreased by 8.7 fewer events/h with AD109, corresponding to a model-based 55.6% reduction from baseline vs 19.1% with placebo (P < .0001).

A “somewhat unexpected” finding, Strollo said, was that AD109 treatment was associated with a 70% reduction in the proportion of breaths with loud snoring compared with a 26% decrease in the placebo group.

There was no statistically significant difference in patient-reported fatigue scores between groups.

Oxygenation improved across all sleep stages, reflecting greater stability in the upper airway throughout the night, the authors noted. AD109 also lessened both the loudness and length of snoring, common signs of airway vibration and blockage, aligning with the drug’s mechanism of increasing airway muscle tone to keep the airway open during sleep.

The authors added a caveat, “While these results demonstrate statistically significant reductions in AHI, the magnitude of change should be interpreted in the context of a population predominantly composed of patients with mild-to-moderate OSA.”

Safety Assessment

The most common adverse events associated with treatment were dry mouth, nausea, insomnia, and urinary hesitation. There were no serious treatment-related adverse events reported in the study. Overall, 21% of participants on AD109 and 3% on placebo discontinued therapy by week 26 because of adverse events, most commonly for insomnia, urinary hesitation, and nausea.

AD109 treatment was also associated with a 1.4 mm Hg increase in blood pressure and a 3.6 beats/min increase in heart rate compared with placebo, which investigators said are known pharmacologic effects of norepinephrine reuptake inhibitors. There were also reductions in REM sleep associated with treatment.

Future Implications

The potential for a pill to improve some of the mechanisms driving OSA raises the possibility of combining this therapy with other treatments in the future, the authors noted. For example, AD109 could be paired with tirzepatide or sulthiame to reduce OSA effects through multiple pathways.

“As more therapeutic options emerge,” the authors added, “the field is expected to move beyond a one-treatment-fits-all paradigm and toward personalized, mechanism-based treatment strategies that expand the number of patients who can achieve durable control of OSA.”

Apnimed sponsored this study. Strollo disclosed serving as a consultant for Apnimed, Inspire Medical Systems, Cryosa, SomnoMed, Philips Respironics, WhisperSom, Biologix, Emmi Solutions, ZOLL Medical Corporation, Restora, and XII Medical; receiving grant support through his institution from Resmed, Inspire Medical Systems, and ZOLL Medical Corporation; and serving as a chair of data and safety monitoring board for the ADIPOSA Study.

Damian McNamara is a freelance contributor to Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. Damian has a BA in chemistry and an MA in science, health and environmental reporting/journalism.